An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics

被引：449

作者：

Angelidis, Ilias ^{[1
,2
]}

Simon, Lukas M. ^{[3
]}

Fernandez, Isis E. ^{[1
,2
]}

Strunz, Maximilian ^{[1
,2
]}

Mayr, Christoph H. ^{[1
,2
]}

Greiffo, Flavia R. ^{[1
,2
]}

Tsitsiridis, George ^{[3
]}

Ansari, Meshal ^{[1
,2
,3
]}

Graf, Elisabeth ^{[4
]}

Strom, Tim-Matthias ^{[4
]}

Nagendran, Monica ^{[5
]}

Desai, Tushar ^{[5
]}

Eickelberg, Oliver ^{[6
]}

Mann, Matthias ^{[7
]}

Theis, Fabian J. ^{[3
,8
]}

Schiller, Herbert B. ^{[1
,2
]}

机构：

[1] Helmholtz Zentrum Munchen, Inst Lung Biol & Dis, D-85764 Munich, Germany

[2] German Ctr Lung Res DZL, D-85764 Munich, Germany

[3] Helmholtz Zentrum Munchen, Inst Computat Biol, D-85764 Munich, Germany

[4] Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Munich, Germany

[5] Stanford Univ, Sch Med, Inst Stem Cell Biol & Regenerat Med, Dept Internal Med,Div Pulm & Crit Care, Stanford, CA 94305 USA

[6] Univ Colorado, Dept Med, Div Resp Sci & Crit Care Med, Aurora, CO 80045 USA

[7] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Munich, Germany

[8] Tech Univ Munich, Dept Math, D-85748 Munich, Germany

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

欧盟地平线“2020”;

关键词：

GENE-EXPRESSION; RNA-SEQ; SPATIAL TRANSCRIPTOMICS; MECHANISMS; BETA; DYSFUNCTION; HALLMARKS; DISEASES; DECORIN; SITE;

D O I：

10.1038/s41467-019-08831-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Aging promotes lung function decline and susceptibility to chronic lung diseases, which are the third leading cause of death worldwide. Here, we use single cell transcriptomics and mass spectrometry-based proteomics to quantify changes in cellular activity states across 30 cell types and chart the lung proteome of young and old mice. We show that aging leads to increased transcriptional noise, indicating deregulated epigenetic control. We observe cell type-specific effects of aging, uncovering increased cholesterol biosynthesis in type-2 pneumocytes and lipofibroblasts and altered relative frequency of airway epithelial cells as hallmarks of lung aging. Proteomic profiling reveals extracellular matrix remodeling in old mice, including increased collagen IV and XVI and decreased Fraser syndrome complex proteins and collagen XIV. Computational integration of the aging proteome with the single cell transcriptomes predicts the cellular source of regulated proteins and creates an unbiased reference map of the aging lung.

引用

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